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Predictors and outcomes of cardiac complications following elective coronary bypass grafting. 择期冠状动脉旁路移植术后心脏并发症的预测因素和结果。
Pub Date : 1999-11-01 DOI: 10.1046/j.1525-1381.1999.99130.x
M Charlson, K H Krieger, J C Peterson, J Hayes, O W Isom

Our objective was to determine the predictors of cardiac complications among a cohort of elective coronary artery bypass graft (CABG) surgery patients and to determine the relationship of such complications to subsequent quality of life and symptoms. A total of 248 patients were enrolled and 237 completed 6 month follow-up. The combined rate of both major and minor cardiac complications was 9.7% (n = 24). Patients in this study were evaluated preoperatively, monitored intraoperatively, followed immediately postoperatively and at 6 months. Major cardiac complications accounted for 3.6% (n = 9) and minor complications for 6% (n = 15). Using multivariable logistic regression analysis, the predictors of major cardiac complications were receiving diuretics preoperatively (p = .01) and increased time during cross-clamping (p = .006). At 6 months after surgery, 19% of the patients with postoperative cardiac complications experienced worsening of symptoms, in contrast to only 8% of those without cardiac complications (p = .03). We concluded that patients who were on preoperative diuretics and those who had longer cross-clamp times were at higher risk of cardiac complications. The majority of patients who had acute cardiac complications had improved function and symptoms at 6 months postoperatively.

我们的目的是确定选择性冠状动脉旁路移植术(CABG)患者心脏并发症的预测因素,并确定这些并发症与随后的生活质量和症状的关系。共有248名患者入组,237名患者完成了6个月的随访。主要和次要心脏并发症合并发生率为9.7% (n = 24)。本研究中的患者术前评估,术中监测,术后和6个月后立即随访。主要心脏并发症占3.6% (n = 9),轻微并发症占6% (n = 15)。采用多变量logistic回归分析,主要心脏并发症的预测因素是术前使用利尿剂(p = 0.01)和交叉夹持时间增加(p = 0.006)。术后6个月,有心脏并发症的患者中有19%出现症状恶化,而无心脏并发症的患者中只有8%出现症状恶化(p = .03)。我们得出结论,术前使用利尿剂和交叉钳夹时间较长的患者心脏并发症的风险较高。大多数有急性心脏并发症的患者在术后6个月功能和症状得到改善。
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引用次数: 14
Physiology and pathophysiology of nitric oxide in chronic renal disease. 慢性肾脏疾病中一氧化氮的生理和病理生理。
Pub Date : 1999-11-01 DOI: 10.1046/j.1525-1381.1999.99256.x
M Noris, G Remuzzi

Nitric oxide (NO), an L-arginine derivative, exerts a variety of renal and extrarenal physiological and pathophysiological effects. NO is generated by three isoforms of nitric oxide synthases (NOS): two acutely responsive, constitutive isoforms, neuronal NOS (nNOS) and endothelial NOS (ecNOS), and the slower, more persistent, inducible NOS (iNOS). NO regulates glomerular ultrafiltration; tubular reabsorption, and intrarenal renin secretion. A number of recent studies, most of them in the experimental model of renal mass reduction (RMR) in rats, have raised the hypothesis that an impaired NO synthetic pathway could have a key role in mediating the complex renal hemodynamic and nonhemodynamic disorders associated with the progression of renal disease. Thus, kidneys from rats with RMR produce less NO than normal rats, and NO generation negatively correlates with markers of renal damage. The abnormality is due to a defect in iNOS in the kidney. Data are also available showing that drugs capable of enhancing renal NO activity may be renoprotective in a variety of experimental renal diseases, particularly those characterized by derangements of glomerular hemodynamics. Fewer studies are available in humans and these have shown less than conclusive results.

一氧化氮(NO)是一种l -精氨酸衍生物,具有多种肾脏和肾外生理和病理生理作用。一氧化氮合成酶(NOS)由三种亚型产生:两种急性反应的组成型亚型,神经元NOS (nNOS)和内皮NOS (ecNOS),以及更慢、更持久的诱导型NOS (iNOS)。NO调节肾小球超滤;肾小管重吸收和肾内肾素分泌。最近的一些研究,大多数是在大鼠肾团块减少(RMR)的实验模型中,提出了一个假设,即一氧化氮合成途径受损可能在介导与肾脏疾病进展相关的复杂肾脏血流动力学和非血流动力学疾病中起关键作用。因此,RMR大鼠肾脏产生的NO比正常大鼠少,并且NO的产生与肾损伤标志物呈负相关。这种异常是由于肾脏的iNOS缺陷造成的。也有数据显示,能够增强肾NO活性的药物可能对多种实验性肾脏疾病,特别是肾小球血流动力学紊乱的肾脏疾病具有肾保护作用。对人类的研究较少,这些研究也没有得出结论性的结果。
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引用次数: 46
Human retroviruses: their role in cancer. 人类逆转录病毒:它们在癌症中的作用
Pub Date : 1999-11-01 DOI: 10.1046/j.1525-1381.1999.99210.x
W A Blattner

Viruses are etiologically linked to approximately 20% of all malignancies worldwide. Retroviruses account for approximately 8%-10% of the total. For human T-cell leukemia virus 1 (HTLV-I), the viral regulatory tax gene product is responsible for enhanced transcription of viral and cellular genes that promote cell growth by stimulating various growth factors and through dysregulation of cellular regulatory suppressor genes, such as p53. After a long latent period, adult T-cell leukemia/lymphoma (ATL) occurs in 1 per 1000 carriers per year, resulting in 2500-3000 cases per year worldwide and over half of the adult lymphoid malignancies in endemic areas. Human immunodeficiency virus 1 (HIV-1) accounts for a significant cancer burden, and its transactivating regulatory protein Tat enhances direct and indirect cytokine and immunological dysregulation to cause diverse cancers. Kaposi's sarcoma (KS) is a very rare tumor except after HIV-1 infection, when its incidence is greatly amplified reaching seventy thousand-fold in HIV-infected homosexual men. Human herpesvirus 8 (HHV-8), which is also known as Kaposi's sarcoma-associated virus (KSHV), is a necessary but not sufficient etiological factor in KS. The dramatic decline of KS since the introduction of highly active antiretroviral therapy (HAART) could be due to suppression of HIV-1 tat. B-cell non-Hodgkin's lymphoma occurs as their first acquired immunodeficiency syndrome-defining diagnosis in 3%-4% of HIV-infected patients. Hodgkin's lymphoma is also associated with HIV infection but at a lower risk. Human papillomaviruses are linked to invasive cervical cancer and anogenital cancers among HIV-infected patients. Human retroviruses cause malignancy via direct effects as well as through interactions with other oncogenic herpesviruses and other viruses.

在病因学上,病毒与全世界约20%的恶性肿瘤有关。逆转录病毒约占总数的8%-10%。对于人类t细胞白血病病毒1 (HTLV-I),病毒调控税基因产物负责增强病毒和细胞基因的转录,这些基因通过刺激各种生长因子和细胞调控抑制基因(如p53)的失调来促进细胞生长。成人t细胞白血病/淋巴瘤(ATL)潜伏期长,每年每1000名携带者中发生1例,每年在世界范围内导致2500-3000例病例,在流行地区超过一半的成人淋巴细胞恶性肿瘤。人类免疫缺陷病毒1 (HIV-1)是一个重要的癌症负担,其反激活调节蛋白可增强直接和间接的细胞因子和免疫失调,导致多种癌症。卡波西肉瘤(KS)是一种非常罕见的肿瘤,除了HIV-1感染之后,它的发病率大大增加,在感染hiv的同性恋男性中达到7万倍。人类疱疹病毒8 (HHV-8),也被称为卡波西肉瘤相关病毒(KSHV),是KS的必要但不充分的病因。自从引入高效抗逆转录病毒疗法(HAART)以来,KS的急剧下降可能是由于HIV-1的抑制。在3%-4%的hiv感染患者中,b细胞非霍奇金淋巴瘤是他们的第一个获得性免疫缺陷综合征诊断。霍奇金淋巴瘤也与HIV感染有关,但风险较低。人类乳头瘤病毒与艾滋病毒感染者的侵袭性宫颈癌和肛门生殖器癌有关。人类逆转录病毒通过直接作用以及与其他致癌疱疹病毒和其他病毒的相互作用引起恶性肿瘤。
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引用次数: 76
Heme oxygenase: recent advances in understanding its regulation and role. 血红素加氧酶的调控及其作用的研究进展。
K K Elbirt, H L Bonkovsky

Heme oxygenase (HO) is responsible for the physiological breakdown of heme into equimolar amounts of biliverdin, carbon monoxide, and iron. Three isoforms (HO-1, HO-2, and HO-3) have been identified. HO-1 is ubiquitous and its mRNA and activity can be increased several-fold by heme, other metalloporphyrins, transition metals, and stimuli that induce cellular stress. HO-1 is recognized as a major heat shock/stress response protein. Recent work from our laboratory has demonstrated several potential consensus regulatory elements in the 5'-untranslated region (UTR) of HO-1, including activator protein 1 (AP-1), metal responsive element (MRE), oncogene c-myc/max heterodimer binding site (Myc/Max), antioxidant response element (ARE), and GC box binding (Sp1) sites. Using deletion-reporter gene constructs, we have mapped sites that mediate the arsenite-dependent induction of HO-1, and we have shown that components of the extracellular signal-regulated kinase (ERK) and p38 (a homologue of the yeast HOG1 kinase), but not c-jun N-terminal kinase (JNK), mitogen-activated protein (MAP) kinase pathways are involved in arsenite-dependent upregulation. In contrast, HO-2 is present chiefly in the brain and testes and is virtually uninducible. HO-3 has very low activity; its physiological function probably involves heme binding. Products of the HO reaction have important effects: carbon monoxide is a potent vasodilator, which is thought to play a key role in the modulation of vascular tone, especially in the liver under physiological conditions, and in many organs under "stressful" conditions associated with HO-1 induction. Biliverdin and its product bilirubin, formed in most mammals, are potent antioxidants. In contrast, "free" iron increases oxidative stress and regulates the expression of many mRNAs (e.g., DCT-1, ferritin, and transferrin receptor) by affecting the conformation of iron regulatory protein (IRP)-1 and its binding to iron regulatory elements (IREs) in the 5'- or 3'-UTRs of the mRNAs.

血红素加氧酶(HO)负责将血红素生理分解成等摩尔量的胆绿素、一氧化碳和铁。已鉴定出三种亚型(HO-1、HO-2和HO-3)。HO-1是普遍存在的,其mRNA和活性可通过血红素、其他金属卟啉、过渡金属和诱导细胞应激的刺激增加数倍。HO-1被认为是主要的热休克/应激反应蛋白。我们实验室最近的工作已经证明了HO-1的5'-非翻译区(UTR)中有几个潜在的共识调控元件,包括激活蛋白1 (AP-1)、金属响应元件(MRE)、癌基因c-myc/max异二聚体结合位点(Myc/ max)、抗氧化反应元件(ARE)和GC盒结合位点(Sp1)。使用缺失报告基因构建,我们绘制了介导亚砷酸盐依赖性HO-1诱导的位点,并且我们已经证明细胞外信号调节激酶(ERK)和p38(酵母HOG1激酶的同源物)的成分,而不是c-jun n末端激酶(JNK),丝裂原活化蛋白(MAP)激酶途径参与亚砷酸盐依赖性上调。相反,HO-2主要存在于大脑和睾丸中,实际上是不可诱导的。HO-3活性很低;其生理功能可能与血红素结合有关。HO反应的产物具有重要的作用:一氧化碳是一种有效的血管扩张剂,被认为在血管张力的调节中起关键作用,特别是在生理条件下的肝脏,以及在与HO-1诱导相关的“应激”条件下的许多器官。胆绿素及其产物胆红素在大多数哺乳动物体内形成,是有效的抗氧化剂。相反,“游离”铁通过影响铁调节蛋白(IRP)-1的构象及其在mrna的5′-或3′- utr中与铁调节元件(IREs)的结合,增加氧化应激并调节许多mrna的表达(如DCT-1、铁蛋白和转铁蛋白受体)。
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引用次数: 0
Presentation of the Kober Medal for 1999 to Jean D. Wilson physician-scientist exemplar. 1999年颁发Kober奖章给Jean D. Wilson医生-科学家典范。
Pub Date : 1999-09-01 DOI: 10.1111/paa.1999.111.5.469
J L Goldstein, M S Brown
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引用次数: 0
Heme oxygenase: recent advances in understanding its regulation and role. 血红素加氧酶的调控及其作用的研究进展。
Pub Date : 1999-09-01 DOI: 10.1111/PAA.1999.111.5.438
K. Elbirt, H. Bonkovsky
Heme oxygenase (HO) is responsible for the physiological breakdown of heme into equimolar amounts of biliverdin, carbon monoxide, and iron. Three isoforms (HO-1, HO-2, and HO-3) have been identified. HO-1 is ubiquitous and its mRNA and activity can be increased several-fold by heme, other metalloporphyrins, transition metals, and stimuli that induce cellular stress. HO-1 is recognized as a major heat shock/stress response protein. Recent work from our laboratory has demonstrated several potential consensus regulatory elements in the 5'-untranslated region (UTR) of HO-1, including activator protein 1 (AP-1), metal responsive element (MRE), oncogene c-myc/max heterodimer binding site (Myc/Max), antioxidant response element (ARE), and GC box binding (Sp1) sites. Using deletion-reporter gene constructs, we have mapped sites that mediate the arsenite-dependent induction of HO-1, and we have shown that components of the extracellular signal-regulated kinase (ERK) and p38 (a homologue of the yeast HOG1 kinase), but not c-jun N-terminal kinase (JNK), mitogen-activated protein (MAP) kinase pathways are involved in arsenite-dependent upregulation. In contrast, HO-2 is present chiefly in the brain and testes and is virtually uninducible. HO-3 has very low activity; its physiological function probably involves heme binding. Products of the HO reaction have important effects: carbon monoxide is a potent vasodilator, which is thought to play a key role in the modulation of vascular tone, especially in the liver under physiological conditions, and in many organs under "stressful" conditions associated with HO-1 induction. Biliverdin and its product bilirubin, formed in most mammals, are potent antioxidants. In contrast, "free" iron increases oxidative stress and regulates the expression of many mRNAs (e.g., DCT-1, ferritin, and transferrin receptor) by affecting the conformation of iron regulatory protein (IRP)-1 and its binding to iron regulatory elements (IREs) in the 5'- or 3'-UTRs of the mRNAs.
血红素加氧酶(HO)负责将血红素生理分解成等摩尔量的胆绿素、一氧化碳和铁。已鉴定出三种亚型(HO-1、HO-2和HO-3)。HO-1是普遍存在的,其mRNA和活性可通过血红素、其他金属卟啉、过渡金属和诱导细胞应激的刺激增加数倍。HO-1被认为是主要的热休克/应激反应蛋白。我们实验室最近的工作已经证明了HO-1的5'-非翻译区(UTR)中有几个潜在的共识调控元件,包括激活蛋白1 (AP-1)、金属响应元件(MRE)、癌基因c-myc/max异二聚体结合位点(Myc/ max)、抗氧化反应元件(ARE)和GC盒结合位点(Sp1)。使用缺失报告基因构建,我们绘制了介导亚砷酸盐依赖性HO-1诱导的位点,并且我们已经证明细胞外信号调节激酶(ERK)和p38(酵母HOG1激酶的同源物)的成分,而不是c-jun n末端激酶(JNK),丝裂原活化蛋白(MAP)激酶途径参与亚砷酸盐依赖性上调。相反,HO-2主要存在于大脑和睾丸中,实际上是不可诱导的。HO-3活性很低;其生理功能可能与血红素结合有关。HO反应的产物具有重要的作用:一氧化碳是一种有效的血管扩张剂,被认为在血管张力的调节中起关键作用,特别是在生理条件下的肝脏,以及在与HO-1诱导相关的“应激”条件下的许多器官。胆绿素及其产物胆红素在大多数哺乳动物体内形成,是有效的抗氧化剂。相反,“游离”铁通过影响铁调节蛋白(IRP)-1的构象及其在mrna的5′-或3′- utr中与铁调节元件(IREs)的结合,增加氧化应激并调节许多mrna的表达(如DCT-1、铁蛋白和转铁蛋白受体)。
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引用次数: 296
Thematic review series. IX: New therapeutic targets for the treatment of heart failure. Introduction. 专题评论系列。九:治疗心力衰竭的新靶点。介绍。
Pub Date : 1999-09-01 DOI: 10.1111/paa.1999.111.5.396
J Ross
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引用次数: 0
Voltage-gated T-type Ca2+ channels and heart failure. 电压门控t型Ca2+通道与心力衰竭。
Pub Date : 1999-09-01 DOI: 10.1111/paa.1999.111.5.429
J P Clozel, E A Ertel, S I Ertel

In the cardiovascular system, two types of voltage-gated Ca2+ channels are present: the L-type and the T-type. Under normal conditions, T-type Ca2+ channels are involved in the maintenance of vascular tone and cardiac automaticity but, since they are not present in contractile myocardial cells, they do not contribute significantly to myocardial contraction. In experimental models of cardiac hypertrophy, myocardial T-type Ca2+ channels are upregulated, which could contribute to the increased incidence of ventricular arrhythmia. In addition, T-type Ca2+ channels participate in the regulation of cell proliferation and neurohormonal secretion; through these pathways, T-type Ca2+ channels might participate in myocardial remodeling. The pathophysiological role of T-type Ca2+ channels in heart failure has been investigated using mibefradil, a Ca2+ antagonist that is 10-50 times more potent at blocking T-type than L-type Ca2+ channels. In contrast with classic L-type Ca2+ channel antagonists, miberfradil appears beneficial in many animal models of heart failure; in particular, it does not exert negative inotropic effects nor does it stimulate the neurohormonal system. Furthermore, in the Pfeffer rat model, blockade of T-type Ca2+ channels with mibefradil is associated with an improved survival rate. In humans, however, major metabolic drug interactions independent of T-type Ca2+ channel blockade made it impossible to determine the efficacy of mibefradil in treating heart failure; indeed, these interactions led to the withdrawal of the drug from the market.

在心血管系统中,存在两种类型的电压门控Ca2+通道:l型和t型。在正常情况下,t型Ca2+通道参与维持血管张力和心脏自动性,但由于它们不存在于收缩性心肌细胞中,因此它们对心肌收缩没有显著贡献。在心肌肥厚的实验模型中,心肌t型Ca2+通道上调,这可能导致室性心律失常的发生率增加。此外,t型Ca2+通道参与调节细胞增殖和神经激素分泌;通过这些途径,t型Ca2+通道可能参与心肌重构。使用mibefradil研究了t型Ca2+通道在心力衰竭中的病理生理作用,这是一种Ca2+拮抗剂,阻断t型Ca2+通道的效力是l型Ca2+通道的10-50倍。与经典的l型Ca2+通道拮抗剂相比,miberfradil在许多心力衰竭动物模型中似乎是有益的;特别是,它不会产生负性肌力作用,也不会刺激神经激素系统。此外,在Pfeffer大鼠模型中,米贝弗拉迪阻断t型Ca2+通道与提高生存率有关。然而,在人类中,独立于t型Ca2+通道阻断的主要代谢药物相互作用使得无法确定米贝替拉治疗心力衰竭的疗效;事实上,这些相互作用导致这种药物从市场上撤出。
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引用次数: 43
Myeloperoxidase. 髓过氧物酶。
Pub Date : 1999-09-01 DOI: 10.1111/paa.1999.111.5.383
S J Klebanoff

Phagocytes respond to stimulation with a burst of oxygen consumption, and much, if not all, of the extra oxygen consumed in the respiratory burst is converted first to the superoxide anion and then to hydrogen peroxide (H2O2). Myeloperoxidase (MPO), which is released from cytoplasmic granules of neutrophils and monocytes by a degranulation process, reacts with the H2O2 formed by the respiratory burst to form a complex that can oxidize a large variety of substances. Among the latter is chloride, which is oxidized initially to hypochlorous acid, with the subsequent formation of chlorine and chloramines. These products of the MPO-H2O2-chloride system are powerful oxidants that can have profound biological effects. The primary function of neutrophils is the phagocytosis and destruction of microorganisms, and the release of MPO and H2O2 into the phagosome containing the ingested microorganism generally leads to a rapid microbicidal effect. Neutrophils from patients with chronic granulomatous disease (CGD) have a microbicidal defect that is associated with the absence of a respiratory burst and, thus, H2O2 production. Neutrophils from patients with a hereditary MPO deficiency, who lack MPO, also have a microbicidal defect, although it is not as severe as that seen in CGD. MPO and H2O2 also can be released to the outside of the cell where a reaction with chloride can induce damage to adjacent tissue and, thus, contribute to the pathogenesis of disease. It has been suggested that pulmonary injury, renal glomerular damage, and the initiation of atherosclerotic lesions may be caused by the MPO system.

吞噬细胞对刺激的反应是消耗大量的氧气,而在呼吸爆发中消耗的额外氧气,如果不是全部的话,大部分首先转化为超氧阴离子,然后转化为过氧化氢(H2O2)。髓过氧化物酶(MPO)由中性粒细胞和单核细胞的细胞质颗粒在脱粒过程中释放出来,与呼吸爆发形成的H2O2反应形成复合物,可以氧化多种物质。后者是氯化物,它最初被氧化成次氯酸,随后形成氯和氯胺。这些mpo - h2o2 -氯化物体系的产物是强大的氧化剂,具有深远的生物效应。中性粒细胞的主要功能是吞噬和破坏微生物,将MPO和H2O2释放到含有摄入微生物的吞噬体中,通常会产生快速的杀微生物作用。慢性肉芽肿病(CGD)患者的中性粒细胞有杀微生物缺陷,这与没有呼吸爆发和H2O2产生有关。来自遗传性MPO缺乏症患者的中性粒细胞(缺乏MPO)也有杀微生物缺陷,尽管不像CGD那样严重。MPO和H2O2也可以释放到细胞外,在那里与氯化物反应可引起邻近组织的损伤,从而促进疾病的发病。有研究表明,肺损伤、肾小球损伤和动脉粥样硬化病变的起始可能是由MPO系统引起的。
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引用次数: 11
Oxygen-independent microbicidal mechanisms of phagocytes. 吞噬细胞不依赖氧的杀微生物机制。
Pub Date : 1999-09-01 DOI: 10.1111/paa.1999.111.5.390
T Ganz

The principal biological function of phagocytic cells is the destruction of invading microorganisms. Following phagocytosis, microbes are exposed to multiple antimicrobial substances ranging in complexity from simple oxygen radicals to large proteins. These substances disrupt various microbial structures and eventually kill and digest most of the invaders. This review is focused on oxygen-independent microbicidal mechanisms in granulocytes and macrophages.

吞噬细胞的主要生物学功能是消灭入侵的微生物。在吞噬作用之后,微生物暴露于多种抗菌物质中,从简单的氧自由基到大的蛋白质。这些物质破坏各种微生物结构,最终杀死并消化大部分入侵者。本文综述了粒细胞和巨噬细胞中不依赖氧的杀微生物机制。
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引用次数: 33
期刊
Proceedings of the Association of American Physicians
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